Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide and the incidence in the United States is increasing. It has been estimated that the number of cases of HCC will continue to increase by 81% (from a baseline of about 13,000 a year) by the year 2020, primarily due to the hepatitis C (HCV) epidemic. Despite advances in medical technology, the 5-year survival between 1981 and 1998 improved only 3%, likely due to the fact that the majority of patients with HCC are diagnosed at advanced stages leading to an overall 1-year survival of 25% in the United States. Early diagnosis of HCC in patients at risk for liver disease will help improve outcome. N-linked glycosylation changes of specific serum biomarker proteins occur with the development of liver cancer. The specific aims of this grant are focused on developing high affinity binding lectins (carbohydrate binding proteins) that recognize the glycsoylation changes that occur on serum biomarkers of HCC (Specific Aim 1) and using these recombinant lectins in an ELISA based format on archived patient serum samples to test their sensitivity and specificity for predicting liver disease and HCC (Specific Aim 2). PUBLIC HEALTH RELEVANCE: The incidence of hepatocellular carcinoma (HCC) is increasing worldwide with a poor prognosis for survival related to the lack of predictive assays for early detection. Sensitive, specific, non-invasive assays that are predictive for diagnosing HCC in patients at risk for liver disease are urgently needed.